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

Yokoro, C.M.; Pesquero, S.M.S.; Turchetti-Maia, R.M.M.; Francischi, Janetti Nogueira de; Tatsuo, M.A.K.F.

doi:10.1590/s0100-879x2001000300015

Cited by 17 publications

(11 citation statements)

References 18 publications

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“…However, it has also been reported that systemic administration of non-hypnotic doses of ethanol and barbiturates to rats results in reduction of tail-flick latency and this is abolished by non-convulsant doses of the GABA A receptor channel blocker picrotoxin, indicating involvement of GABAergic mechanisms in the mediation of ethanol-induced hyperalgesia [22]. Other studies have demonstrated that intracerebroventricular, but not intrathecal administration of these drugs induces a similar hyperalgesic state that is also reversed by a GABA A receptor blocker [45,46]. These results suggested that ethanol and some barbiturates might induce pain hypersensitivity (hyperalgesia) through acting on GABA A receptors at the supraspinal level, while they induce antinociception (analgesia) through acting on GABA A receptors at the spinal level.…”

Section: Where and How Ethanol Modulates Pain?mentioning

confidence: 92%

Ethanol Increases Mechanical Pain Sensitivity in Rats via Activation of GABAA Receptors in Medial Prefrontal Cortex

Geng

Wang

et al. 2016

Neurosci. Bull.

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Ethanol is widely known for its ability to cause dramatic changes in emotion, social cognition, and behavior following systemic administration in humans. Human neuroimaging studies suggest that alcohol dependence and chronic pain may share common mechanisms through amygdala-medial prefrontal cortex (mPFC) interactions. However, whether acute administration of ethanol in the mPFC can modulate pain perception is unknown. Here we showed that bilateral microinjections of ethanol into the prelimbic and infralimbic areas of the mPFC lowered the bilateral mechanical pain threshold for 48 h without influencing thermal pain sensitivity in adult rats. However, bilateral microinjections of artificial cerebrospinal fluid into the mPFC or bilateral microinjections of ethanol into the dorsolateral PFC (also termed as motor cortex area 1 in Paxinos and Watson's atlas of The Rat Brain. Elsevier Academic Press, Amsterdam, 2005) failed to do so, suggesting regional selectivity of the effects of ethanol. Moreover, bilateral microinjections of ethanol did not change the expression of either pro-apoptotic (caspase-3 and Bax) or anti-apoptotic (Bcl-2) proteins, suggesting that the dose was safe and validating the method used in the current study. To determine whether c-aminobutyric acid A (GABA A ) receptors are involved in mediating the ethanol effects, muscimol, a selective GABA A receptor agonist, or bicuculline, a selective GABA A receptor antagonist, was administered alone or co-administered with ethanol through the same route into the bilateral mPFC. The results showed that muscimol mimicked the effects of ethanol while bicuculline completely reversed the effects of ethanol and muscimol. In conclusion, ethanol increases mechanical pain sensitivity through activation of GABA A receptors in the mPFC of rats.

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Section: Where and How Ethanol Modulates Pain?mentioning

confidence: 92%

Ethanol Increases Mechanical Pain Sensitivity in Rats via Activation of GABAA Receptors in Medial Prefrontal Cortex

Geng

Wang

et al. 2016

Neurosci. Bull.

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“…PB may directly activate the GABA A receptor [96]. The actions of PB through these effects may reduce anxiety, promote sleep, induce general anesthesia, and act as an effective control of generalized and partial tonic–clonic seizures [97,98]. PB was the World Health Organization’s first-line AED in developing countries because of its low cost and effectiveness in the treatment of seizures.…”

Section: Introductionmentioning

confidence: 99%

The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism

Fan

Lee

Chang

et al. 2016

IJMS

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Epilepsy is a common neurological disorder worldwide and anti-epileptic drugs (AEDs) are always the first choice for treatment. However, more than 50% of patients with epilepsy who take AEDs have reported bone abnormalities. Cytochrome P450 (CYP450) isoenzymes are induced by AEDs, especially the classical AEDs, such as benzodiazepines (BZDs), carbamazepine (CBZ), phenytoin (PT), phenobarbital (PB), and valproic acid (VPA). The induction of CYP450 isoenzymes may cause vitamin D deficiency, hypocalcemia, increased fracture risks, and altered bone turnover, leading to impaired bone mineral density (BMD). Newer AEDs, such as levetiracetam (LEV), oxcarbazepine (OXC), lamotrigine (LTG), topiramate (TPM), gabapentin (GP), and vigabatrin (VB) have broader spectra, and are safer and better tolerated than the classical AEDs. The effects of AEDs on bone health are controversial. This review focuses on the impact of AEDs on growth and bone metabolism and emphasizes the need for caution and timely withdrawal of these medications to avoid serious disabilities.

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“…By suppressing descending inhibitory systems, pentobarbital may facilitate central sensitization and the development of pain after nociceptive input. Supporting this, others showed that barbiturates can induce enhanced pain (hyperalgesia) on a number of measures (Franklin and Abbott 1993;Yokoro et al 2001). This hyperalgesia may result from changes in dorsal horn neurons, which change response profiles to noxious stimuli from low threshold to wide dynamic range neurons after pentobarbital administration in intact animals (Collins and Ren 1987).…”

Section: Discussionmentioning

confidence: 87%

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

Cited by 17 publications

References 18 publications

Ethanol Increases Mechanical Pain Sensitivity in Rats via Activation of GABAA Receptors in Medial Prefrontal Cortex

Ethanol Increases Mechanical Pain Sensitivity in Rats via Activation of GABAA Receptors in Medial Prefrontal Cortex

The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism

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

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