Morphine inhibits acid-sensing ion channel currents in rat dorsal root ganglion neurons

Cai, Qi; Qiu, Chun‐Yu; Qiu, Fang; Liu, Tingting; Qu, Zu-Wei; Liu, Yumin; Hu, Wang‐Ping

doi:10.1016/j.brainres.2014.01.042

Cited by 36 publications

(23 citation statements)

References 39 publications

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“…Our results are difficult to reconcile with those previously reported in rat DRG neurons in which morphine or [ d ‐Ala2,N‐Me‐Phe4,Gly5‐ol]‐enkephalin (DAMGO) blocked the peak ASIC current via MOR stimulation (Cai et al . ). The opioid‐mediated block was shown to be PTX‐ and naloxone‐sensitive.…”

Section: Discussionmentioning

confidence: 97%

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Endomorphins potentiate acid‐sensing ion channel currents and enhance the lactic acid‐mediated increase in arterial blood pressure: effects amplified in hindlimb ischaemia

Farrag

Drobish

Puhl

et al. 2017

The Journal of Physiology

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Chronic muscle ischaemia leads to accumulation of lactic acid and other inflammatory mediators with a subsequent drop in interstitial pH. Acid-sensing ion channels (ASICs), expressed in thin muscle afferents, sense the decrease in pH and evoke a pressor reflex known to increase mean arterial pressure. The naturally occurring endomorphins are also released by primary afferents under ischaemic conditions. We examined whether high affinity mu opioid receptor (MOR) agonists, endomorphin-1 (E-1) and -2 (E-2), modulate ASIC currents and the lactic acid-mediated pressor reflex. In rat dorsal root ganglion (DRG) neurons, exposure to E-2 in acidic solutions significantly potentiated ASIC currents when compared to acidic solutions alone. The potentiation was significantly greater in DRG neurons isolated from rats whose femoral arteries were ligated for 72 h. Sustained ASIC current potentiation was also observed in neurons pretreated with pertussis toxin, an uncoupler of G proteins and MOR. The endomorphin-mediated potentiation was a result of a leftward shift of the activation curve to higher pH values and a slight shift of the inactivation curve to lower pH values. Intra-arterial co-administration of lactic acid and E-2 led to a significantly greater pressor reflex than lactic acid alone in the presence of naloxone. Finally, E-2 effects were inhibited by pretreatment with the ASIC3 blocker APETx2 and enhanced by pretreatment with the ASIC1a blocker psalmotoxin-1. These findings have uncovered a novel role of endomorphins by which the opioids can enhance the lactic acid-mediated reflex increase in arterial pressure that is MOR stimulation-independent and APETx2-sensitive.

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Section: Discussionmentioning

confidence: 97%

“…In that study, the effect of opioids on the sustained ASIC currents was not examined (Cai et al . ). As mentioned above, under our recording conditions, the effect of endomorphins on peak ASIC currents was inconsistent.…”

Section: Discussionmentioning

confidence: 97%

Endomorphins potentiate acid‐sensing ion channel currents and enhance the lactic acid‐mediated increase in arterial blood pressure: effects amplified in hindlimb ischaemia

Farrag

Drobish

Puhl

et al. 2017

The Journal of Physiology

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“…Increases in pC0 2 drive respiration in part via the carbonic anhydrase-catalyzed conversion of CO 2 plus H 2 O to H 2 CO 3 , which spontaneously decomposes to HCO 3 - and H+ (Guyenet et al, 2010). Although direct evidence in the brain is lacking, morphine inhibits erythrocyte carbonic anhydrase (Coban et al, 2007) and inhibits acidsensing ion channels (ASICs) in rat dorsal root neurons (Cai et al, 2014). Furthermore, morphine increases secretion of melatonin (Esposti et al, 1988), which attenuates CB chemoreceptor response of rats to hypercapnic acidosis (Tjong et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Bilateral carotid sinus nerve transection exacerbates morphine-induced respiratory depression

Baby¹,

Gruber²,

Young

et al. 2018

European Journal of Pharmacology

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Opioid-induced respiratory depression (OIRD) involves decreased sensitivity of ventilatory control systems to decreased blood levels of oxygen (hypoxia) and elevated levels of carbon dioxide (hypercapnia). Understanding the sites and mechanisms by which opioids elicit respiratory depression is pivotal for finding novel therapeutics to prevent and/or reverse OIRD. To examine the contribution of carotid body chemoreceptors OIRD, we used whole-body plethysmography to evaluate hypoxic (HVR) and hypercapnic (HCVR) ventilatory responses including changes in frequency of breathing, tidal volume, minute ventilation and inspiratory drive, after intravenous injection of morphine (10 mg/kg) in sham-operated (SHAM) and in bilateral carotid sinus nerve transected (CSNX) Sprague-Dawley rats. In SHAM rats, morphine produced sustained respiratory depression (e.g., decreases in tidal volume, minute ventilation and inspiratory drive) and reduced the HVR and HCVR responses. Unexpectedly, morphine-induced suppression of HVR and HCVR were substantially greater in CSNX rats than in SHAM rats. This suggests that morphine did not compromise the function of the carotid body-chemoafferent complex and indeed, that the carotid body acts to defend against morphine-induced respiratory depression. These data are the first in vivo evidence that carotid body chemoreceptor afferents defend against rather than participate in OIRD in conscious rats. As such, drugs that stimulate ventilation by targeting primary glomus cells and/or chemoafferent terminals in the carotid bodies may help to alleviate OIRD.

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“…18,19,23 ASICs can respond to acidic pH (below pH 7.0) in the DRG and their expression is upregulated in the DRG and spinal cord during inflammation. 24,25 In TG neurons, the protein expression of ASIC1, ASIC2a and ASIC3 was obviously enhanced in the formalin model and the amplitude and current density of ASIC-like currents also increased after formalin injection. In addition, different ASIC blockers partially abolished this effect.…”

Section: Discussionmentioning

confidence: 99%

“…In the inflammatory state, the extracellular pH decreases because of cell damage, immune response, or hypoxic metabolism; then, acid‐sensitive channels are activated and perceive the acidic microenvironment, contributing to inflammatory pain . ASICs can respond to acidic pH (below pH 7.0) in the DRG and their expression is upregulated in the DRG and spinal cord during inflammation . In TG neurons, the protein expression of ASIC1, ASIC2a and ASIC3 was obviously enhanced in the formalin model and the amplitude and current density of ASIC‐like currents also increased after formalin injection.…”

Section: Discussionmentioning

confidence: 99%

Acid‐sensing ion channels in trigeminal ganglion neurons innervating the orofacial region contribute to orofacial inflammatory pain

Peng

Zhou

et al. 2016

Clin Exp Pharma Physio

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Orofacial pain is a common clinical symptom that is accompanied by tooth pain, migraine and gingivitis. Accumulating evidence suggests that acid-sensing ion channels (ASICs), especially ASIC3, can profoundly affect the physiological properties of nociception in peripheral sensory neurons. The aim of this study is to examine the contribution of ASICs in trigeminal ganglion (TG) neurons to orofacial inflammatory pain. A Western blot (WB), immunofluorescence assay of labelled trigeminal ganglion neurons, orofacial formalin test, cell preparation and electrophysiological experiments are performed. This study demonstrated that ASIC1, ASIC2a and ASIC3 are highly expressed in TG neurons innervating the orofacial region of rats. The amplitude of ASIC currents in these neurons increased 119.72% (for ASIC1-like current) and 230.59% (for ASIC3-like current) in the formalin-induced orofacial inflammatory pain model. In addition, WB and immunofluorescence assay demonstrated a significantly augmented expression of ASICs in orofacial TG neurons during orofacial inflammation compared with the control group. The relative protein density of ASIC1, ASIC2a and ASIC3 also increased 58.82 ± 8.92%, 45.30 ± 11.42% and 55.32 ± 14.71%, respectively, compared with the control group. Furthermore, pharmacological blockade of ASICs and genetic deletion of ASIC1 attenuated the inflammation response. These findings indicate that peripheral inflammation can induce the upregulation of ASICs in TG neurons, causing orofacial inflammatory pain. Additionally, the specific inhibitor of ASICs may have a significant analgesic effect on orofacial inflammatory pain.

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Morphine inhibits acid-sensing ion channel currents in rat dorsal root ganglion neurons

Cited by 36 publications

References 39 publications

Endomorphins potentiate acid‐sensing ion channel currents and enhance the lactic acid‐mediated increase in arterial blood pressure: effects amplified in hindlimb ischaemia

Endomorphins potentiate acid‐sensing ion channel currents and enhance the lactic acid‐mediated increase in arterial blood pressure: effects amplified in hindlimb ischaemia

Bilateral carotid sinus nerve transection exacerbates morphine-induced respiratory depression

Acid‐sensing ion channels in trigeminal ganglion neurons innervating the orofacial region contribute to orofacial inflammatory pain

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