GABAergic modulation of nociceptive threshold: effects of THIP and bicuculline microinjected in the ventral medulla of the rat

Drower, Edward J.; Hammond, Donna L.

doi:10.1016/0006-8993(88)91570-3

Cited by 95 publications

(37 citation statements)

References 27 publications

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“…However, this result is supported by previous studies performed in animals and humans. In animals, BZDs have been shown to antagonise opioid analgesia [15,16], and in humans the BZD antagonist flumazenil has been shown to enhance Anaesthesia ...................................................................................................................................................................................................................…”

Section: Discussionmentioning

confidence: 99%

Effect of pre‐operative anxiolysis on postoperative pain response in patients undergoing total abdominal hysterectomy

Caumo¹,

Hidalgo²,

Schmidt

et al. 2002

Anaesthesia

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SummaryIn a double blind, placebo-controlled trial, we have assessed the effects of pre-operative anxiolysis on postoperative pain scores in 112 ASA I-II women, aged 18-65 years, scheduled to undergo total abdominal hysterectomy. Subjects were randomly allocated to receive either oral diazepam 10 mg (n ¼ 56) or placebo (n ¼ 56) pre-operatively. Postoperative anxiety, pain scores, analgesic consumption, and sedation were evaluated at several time points during the first 24 h following surgery. Postoperative pain scores were found to be significantly higher in the diazepam group. Trait and state anxiety showed a significant effect on pain scores, independent of the treatment group. No difference was found between the groups in morphine consumption, but there was a significant reduction in morphine consumption with time. The association between anxiety and postoperative pain is well known [1][2][3], and despite the routine use of benzodiazepines (BZD), there is little clinical evidence available on the effects of premedication on postoperative outcomes such as pain scores and analgesic consumption. The effect of premedication has been mainly assessed in relation to: heart rate; blood pressure; neuroendocrine changes; quality of induction of anaesthesia; amnesia and anxiety [4]. It is important that we are aware of the impact that pre-operative anxiety may have on postoperative outcomes [5].The relationship between pre-operative anxiety and postoperative pain is of particular importance, since several pharmacological and non-pharmacological options are available to treat pre-operative anxiety [6]. If increased pre-operative anxiety is associated with increased postoperative pain, then reducing pre-operative anxiety, could reduce postoperative pain.Therefore, the purpose of this study was to assess the effect of pre-operative anxiolysis on postoperative pain scores based on analgesic consumption and pain scores in patients undergoing total abdominal hysterectomy. Methods

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Section: Discussionmentioning

confidence: 99%

Effect of pre‐operative anxiolysis on postoperative pain response in patients undergoing total abdominal hysterectomy

Caumo¹,

Hidalgo²,

Schmidt

et al. 2002

Anaesthesia

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“…The exact mechanism through which this occurs remains unknown, although the inhibitory neurotransmitter GABA appears to play a major role (Asana and Ogasawara 1981;Olsen and Snowman 1982;Sivam et al 1982). For example, activation of GABA receptors in the NRM was shown to increase responses to noxious stimuli (Drower and Hammond 1988). Pentobarbital may bind to GABA receptors in the NRM, resulting in a disinhibition of systems necessary for pain modulation.…”

Section: Discussionmentioning

confidence: 99%

Exposure to intermittent nociceptive stimulation under pentobarbital anesthesia disrupts spinal cord function in rats

et al. 2007

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Rationale-Spinal cord plasticity can be assessed in spinal rats using an instrumental learning paradigm in which subjects learn an instrumental response, hindlimb flexion, to minimize shock exposure. Prior exposure to uncontrollable intermittent stimulation blocks learning in spinal rats but has no effect if given before spinal transection, suggesting that supraspinal systems modulate nociceptive input to the spinal cord, rendering it less susceptible to the detrimental consequences of uncontrollable stimulation.Objective-The present study examines whether disrupting brain function with pentobarbital blocks descending inhibitory systems that normally modulate nociceptive input, making the spinal cord more sensitive to the adverse effect of uncontrollable intermittent stimulation. Materials and methods-MaleSprague-Dawley rats received uncontrollable intermittent stimulation during pentobarbital anesthesia after (experiment 1) or before (experiment 2) spinal cord transection. They were then tested for instrumental learning at a later time point. Experiment 3 examined whether these manipulations affected nociceptive (thermal) thresholds.Results-Experiment 1 showed that pentobarbital had no effect on the induction of the learning deficit after spinal cord transection. Experiment 2 showed that intact rats anesthetized during uncontrollable intermittent stimulation failed to learn when later transected and tested for instrumental learning. Experiment 3 found that uncontrollable intermittent stimulation induced an antinociception in intact subjects that was blocked by pentobarbital. Conclusions-The results suggest a surgical dose of pentobarbital (50 mg/kg) suppresses supraspinal (experiment 2) but not spinal (experiment 1) systems that modulate nociceptive input to the spinal cord by blocking the antinociception that is induced by this input (experiment 3).

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“…To achieve this, barbiturates bind at the GABA-A receptor increasing the opening time of chloride channels, thus permitting chloride ion entry into the cells (4). In addition, activation of the GABA-A receptor has been associated with pain modulation in the central nervous system (CNS), essentially through the descending inhibitory system (5). However, it is still a matter of discussion in the literature whether barbiturates increase (6,7) or decrease (8,9) the pain threshold.…”

Section: Introductionmentioning

confidence: 99%

“…Some studies have shown that the site of barbiturate binding is close to the site of the neurotransmitter binding in the GABA-A receptor (4,5). On the other hand, the picrotoxin site is inside the channel where it seems to inhibit the entry of the chloride ions into the cell (24).…”

mentioning

confidence: 99%

Acute phenobarbital administration induces hyperalgesia: pharmacological evidence for the involvement of supraspinal GABA-A receptors

Yokoro

Pesquero

Turchetti-Maia

et al. 2001

Braz J Med Biol Res

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The aim of the present study was to determine if phenobarbital affects the nociception threshold. Systemic (1-20 mg/kg) phenobarbital administration dose dependently induced hyperalgesia in the tail-flick, hot-plate and formalin tests in rats and in the abdominal constriction test in mice. Formalin and abdominal constriction tests were the most sensitive procedures for the detection of hyperalgesia in response to phenobarbital compared with the tail-flick and hot-plate tests. The hyperalgesia induced by systemic phenobarbital was blocked by previous administration of 1 mg/kg ip picrotoxin or either 1-2 mg/kg sc or 10 ng icv bicuculline. Intracerebroventricular phenobarbital administration (5 µg) induced hyperalgesia in the tail-flick test. In contrast, intrathecal phenobarbital administration (5 µg) induced antinociception and blocked systemic-induced hyperalgesia in this test. We suggest that phenobarbital may mediate hyperalgesia through GABA-A receptors at supraspinal levels and antinociception through the same kind of receptors at spinal levels.

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GABAergic modulation of nociceptive threshold: effects of THIP and bicuculline microinjected in the ventral medulla of the rat

Cited by 95 publications

References 27 publications

Effect of pre‐operative anxiolysis on postoperative pain response in patients undergoing total abdominal hysterectomy

Effect of pre‐operative anxiolysis on postoperative pain response in patients undergoing total abdominal hysterectomy

Exposure to intermittent nociceptive stimulation under pentobarbital anesthesia disrupts spinal cord function in rats

Acute phenobarbital administration induces hyperalgesia: pharmacological evidence for the involvement of supraspinal GABA-A receptors

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