Rat Periaqueductal Gray Neurons Research Articles

Neural Subtype-dependent Cholinergic Modulation of Neural Activities by Activation of Muscarinic 2 Receptors and G Protein-activated Inwardly Rectifying Potassium Channel in Rat Periaqueductal Gray Neurons

Acetylcholine plays a pivotal role in the regulation of functions such as pain and the sleep and wake cycle by modulating neural activities of the ventrolateral periaqueductal gray (vlPAG). Electrophysiological studies have shown that cholinergic effects are inconsistent among recorded neurons, particularly in the depolarization and hyperpolarization of the resting membrane potential (RMP). This discrepancy may be due to the neural subtype-dependent cholinergic modulation of the RMP. To examine this possibility, we performed whole-cell patch-clamp recordings from subtype-identified neurons using vesicular GABA transporter (VGAT)-Venus × ChAT-TdTomato rats and elucidated cellular mechanisms of cholinergic effects on the RMP. The application of carbachol hyperpolarized the RMP of cholinergic neurons in a dose-dependent manner but had much less of an effect on other neural subtypes, including GABAergic/glycinergic and glutamatergic neurons. Cholinergic hyperpolarization was accompanied by a decrease in input resistance. These cholinergic effects were blocked by AF-DX384 or gallamine and were mimicked by arecaidine but-2-ynyl ester tosylate, suggesting that the carbachol-induced hyperpolarization of the RMP in cholinergic neurons is mediated via M2 receptors. Tertiapin suppressed the carbachol-induced G protein-activated inwardly rectifying potassium channel (GIRK) currents and hyperpolarization of the RMP in cholinergic neurons. Intracellular application of GDP-β-S blocked the carbachol-induced hyperpolarization of the RMP. Neostigmine slowly hyperpolarized the RMP in cholinergic neurons. These results suggest that neural firing of vlPAG cholinergic neurons is suppressed by GIRK currents induced via M2 receptor activation, and this negative feedback regulation of cholinergic neuronal activities can be induced by acetylcholine, which is intrinsically released in the vlPAG.

The Lysophosphatidylinositol Receptor GPR55 Modulates Pain Perception in the Periaqueductal Gray.

Emerging evidence indicates the involvement of GPR55 and its proposed endogenous ligand, lysophosphatidylinositol (LPI), in nociception, yet their role in central pain processing has not been explored. Using Ca(2+) imaging, we show here that LPI elicits concentration-dependent and GPR55-mediated increases in intracellular Ca(2+) levels in dissociated rat periaqueductal gray (PAG) neurons, which express GPR55 mRNA. This effect is mediated by Ca(2+) release from the endoplasmic reticulum via inositol 1,4,5-trisphosphate receptors and by Ca(2+) entry via P/Q-type of voltage-gated Ca(2+) channels. Moreover, LPI depolarizes PAG neurons and upon intra-PAG microinjection, reduces nociceptive threshold in the hot-plate test. Both these effects are dependent on GPR55 activation, because they are abolished by pretreatment with ML-193 [N-(4-(N-(3,4-dimethylisoxazol-5-yl)sulfamoyl)-phenyl)-6,8-dimethyl-2-(pyridin-2-yl)quinoline-4-carboxamide], a selective GPR55 antagonist. Thus, we provide the first pharmacological evidence that GPR55 activation at central levels is pronociceptive, suggesting that interfering with GPR55 signaling in the PAG may promote analgesia.

Ion Channel Modulation in Spinal/Trigeminal Synaptic Plasticity

Ion Channel Modulation in Spinal/Trigeminal Synaptic Plasticity

GABAB receptors resist acute desensitization in both postsynaptic and presynaptic compartments of periaqueductal gray neurons

The ventrolateral midbrain periaqueductal gray (PAG) neurons have been intensively studied because of their pivotal role in the descending pain modulation system. Activation of GABAB receptors, one type of inhibitory G-protein-coupled receptors (GPCRs), in PAG neurons results in both presynaptic and postsynaptic inhibition. Acute desensitization is defined as rapid attenuation of receptor-mediated signaling. Recent studies report that multiple inhibitory GPCRs, including GABAB receptors, resist acute desensitization in the presynaptic but not postsynaptic compartments of certain neurons in mammal brains. In the present study, employing whole-cell voltage-clamp recordings on acute PAG slices from adult rats, we found that GABAB receptors resist acute desensitization to prolonged administration of baclofen (GABAB receptor agonist) in both presynaptic and postsynaptic compartments. The desensitization resistance of postsynaptic GABAB receptors was independent of presynaptic alteration and vice versa. The GABAB receptor-mediated inhibition at inhibitory presynaptic terminals also showed no desensitization. The results suggest that GABAB receptor-mediated inhibition remains functional in both postsynaptic and presynaptic compartments to sustained agonist administration in rat PAG neurons.

Serotonergic modulation of neuronal activity in rat midbrain periaqueductal gray

Serotonin (5-HT) modulates pain and anxiety from within the midbrain periaqueductal gray (PAG). In the present study, the effects of 5-HT- and 5-HT(1/2) subtype-selective ligands on rat PAG neurons were examined using whole cell patch-clamp recordings in brain slices. In voltage clamp, 5-HT produced outward and inward currents in distinct subpopulations of neurons that varied throughout different subregions of the PAG. The 5-HT(1A) agonist R(+)-8-OH-DPAT (1 μM) produced outward currents in subpopulations of PAG neurons. By contrast, sumatriptan (1 μM) and other 5-HT(1B, -D), and (-F) subtype agonists had little or no postsynaptic activity. The 5-HT(2A/C) agonists DOI (3 μM) and TCB-2 (1 μM) produced inward currents in subpopulations of PAG neurons, and DOI enhanced evoked inhibitory postsynaptic currents via a presynaptic mechanism. In current clamp, both R(+)-8-OH-DPAT and sumatriptan produced an excitatory increase in evoked mixed postsynaptic potentials (PSPs). In addition, R(+)-8-OH-DPAT, but not sumatriptan, directly hyperpolarized PAG neurons. By contrast, the 5-HT(2) agonist DOI depolarized subpopulations of neurons and produced an inhibitory decrease in evoked mixed PSPs. These findings indicate that 5-HT(1A) and 5-HT(1B/D) ligands have partly overlapping inhibitory effects on membrane excitability and synaptic transmission within the PAG, which are functionally opposed by 5-HT(2A/C) actions in specific PAG subregions.

Presynaptic Glycine Receptors Increase GABAergic Neurotransmission in Rat Periaqueductal Gray Neurons

The periaqueductal gray (PAG) is involved in the central regulation of nociceptive transmission by affecting the descending inhibitory pathway. In the present study, we have addressed the functional role of presynaptic glycine receptors in spontaneous glutamatergic transmission. Spontaneous EPSCs (sEPSCs) were recorded in mechanically dissociated rat PAG neurons using a conventional whole-cell patch recording technique under voltage-clamp conditions. The application of glycine (100 µM) significantly increased the frequency of sEPSCs, without affecting the amplitude of sEPSCs. The glycine-induced increase in sEPSC frequency was blocked by 1 µM strychnine, a specific glycine receptor antagonist. The results suggest that glycine acts on presynaptic glycine receptors to increase the probability of glutamate release from excitatory nerve terminals. The glycine-induced increase in sEPSC frequency completely disappeared either in the presence of tetrodotoxin or Cd2+, voltage-gated Na+, or Ca2+ channel blockers, suggesting that the activation of presynaptic glycine receptors might depolarize excitatory nerve terminals. The present results suggest that presynaptic glycine receptors can regulate the excitability of PAG neurons by enhancing glutamatergic transmission and therefore play an important role in the regulation of various physiological functions mediated by the PAG.

Postsynaptic mGluR mediated excitation of neurons in midbrain periaqueductal grey

Metabotropic glutamate (mGlu) receptors modulate pain from within the midbrain periaqueductal grey (PAG). In the present study, the postsynaptic mGlu receptor mediated effects on rat PAG neurons were examined using whole-cell patch-clamp recordings in brain slices. The selective group I agonist DHPG (10 μM) produced an inward current in all PAG neurons tested which was associated with a near parallel shift in the current–voltage relationship. By contrast, the group II and III mGlu receptor agonists DCG-IV (1 μM) and l-AP4 (3 μM) produced an outward current in only 10–20% of PAG neurons tested. The DHPG induced current was concentration dependent (EC50 = 1.4 μM), was reduced by the mGlu1 antagonist CPCCOEt (100 μM), and was further reduced by CPCCOEt in combination with the mGlu5 antagonist MPEP (10 μM). The glutamate transport blocker TBOA (30 μM) also produced an inward current, however, this was largely abolished by CNQX (10 μM) plus AP5 (25 μM). Slow EPSCs were evoked following train, but not single shock stimulation, which were enhanced by TBOA (30 μM). The TBOA enhancement of slow EPSCs was abolished by MPEP plus CPCCOEt. These findings indicate that endogenously released glutamate, under conditions in which neurotransmitter spill-over is enhanced, activates group I mGlu receptors to produce excitatory currents within PAG. Thus, postsynaptic group I mGlu receptors have the potential to directly modulate the analgesic, behavioural and autonomic functions of the PAG.This article is part of a Special Issue entitled ‘Metabotropic Glutamate Receptors’.

GABAA receptors facilitate spontaneous glutamate release in rat periaqueductal gray neurons

The functional role of presynaptic γ-aminobutyric acid (GABA)(A) receptors in excitatory glutamatergic transmission was examined in rat periaqueductal gray neurons recorded using a conventional whole-cell patch clamp technique. Muscimol, a GABA(A) receptor agonist, significantly increased the frequency of spontaneous excitatory postsynaptic currents without affecting their amplitude, and this effect was completely blocked by the selective GABA(A) receptor antagonist. The muscimol-induced facilitation of spontaneous excitatory postsynaptic current frequency disappeared either in the presence of tetrodotoxin or Cd. The results suggest that the activation of presynaptic GABA(A) receptors directly depolarizes glutamatergic terminals resulting in the facilitation of spontaneous glutamate release, and that presynaptic GABA(A) receptors play an important role in the regulation of various physiological functions mediated by the periaqueductal gray.

Tolerance to the Antinociceptive Effect of Morphine in the Absence of Short-Term Presynaptic Desensitization in Rat Periaqueductal Gray Neurons

Opioids activate the descending antinociceptive pathway from the ventrolateral periaqueductal gray (vlPAG) by both pre- and postsynaptic inhibition of tonically active GABAergic neurons (i.e., disinhibition). Previous research has shown that short-term desensitization of postsynaptic μ-opioid receptors (MOPrs) in the vlPAG is increased with the development of opioid tolerance. Given that pre- and postsynaptic MOPrs are coupled to different signaling mechanisms, the present study tested the hypothesis that short-term desensitization of presynaptic MOPrs also contributes to opioid tolerance. Twice-daily injections of morphine (5 mg/kg s.c.) for 2 days caused a rightward shift in the morphine dose-response curve on the hot plate test (D(50) = 9.9 mg/kg) compared with saline-pretreated (5.3 mg/kg) male Sprague-Dawley rats. In vitro whole-cell patch-clamp recordings from vlPAG slices revealed that inhibition of evoked inhibitory postsynaptic currents (eIPSCs) by the MOPr-selective agonist [d-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin was decreased in morphine-tolerant (EC(50) = 708 nM) compared with saline-pretreated rats (EC(50) = 163 nM). However, short-term desensitization of MOPr inhibition of eIPSCs was not observed in either saline- or morphine-pretreated rats. Reducing the number of available MOPrs with the irreversible opioid receptor antagonist, β-chlornaltrexamine decreased maximal MOPr inhibition with no evidence of desensitization, indicating that the lack of observed desensitization is not caused by receptor reserve. These results demonstrate that tolerance to the antinociceptive effect of morphine is associated with a decrease in presynaptic MOPr sensitivity or coupling to effectors, but this change is independent of short-term MOPr desensitization.

Presynaptic nicotinic acetylcholine receptors enhance GABAergic synaptic transmission in rat periaqueductal gray neurons

The periaqueductal gray (PAG) is a major component of the descending pain inhibitory pathway, which is related to central analgesia. In the present study, we have investigated the possible roles of presynaptic nicotinic acetylcholine receptors in GABAergic transmission onto PAG neurons. In acutely isolated rat PAG neurons, GABAergic miniature inhibitory postsynaptic currents (mIPSCs) were recorded by use of a whole-cell patch clamp technique. Acetylcholine (30 μM) transiently increased both the frequency and amplitude of GABAergic mIPSCs. However, acetylcholine did not affect the GABA-induced membrane currents. This facilitatory action of acetylcholine disappeared in the presence of mecamylamine, a nonselective nicotinic receptor antagonist, and mimicked by nicotine, a nicotinic receptor agonist. The nicotine-induced increase in mIPSC frequency was completely blocked by dihydro-β-erythroidine, a selective β2-containing nicotinic receptor antagonist, but not methyllycaconitine or α-bungarotoxin, selective α7 nicotinic receptor antagonists. The results suggest that acetylcholine or nicotine acts presynaptic β2-containing nicotinic receptors, presumably α4β2 nicotinic receptors, to enhance spontaneous GABA release onto PAG neurons. The nicotine-induced increase in mIPSC frequency was completely occluded in the presence of Cd 2+, a general voltage-dependent Ca 2+ channels blocker, and in the absence of extracellular Ca 2+ or Na +. The results suggest that presynaptic nicotinic receptors are less permeable to Ca 2+, and that the activation of these receptors depolarizes GABAergic nerve terminals. In conclusion, presynaptic nicotinic receptors would temporally regulate the excitability of PAG neurons being not overexcited and eventually contribute to the cholinergic modulation of output from the PAG.

Presynaptic kainate receptors increase GABAergic neurotransmission in rat periaqueductal gray neurons

Neurons within the periaqueductal gray (PAG) have been implicated in the central regulation of pain signals by affecting the descending inhibitory pathway. Here we report on the functional role of presynaptic kainate receptors within the PAG. Using a conventional whole-cell patch clamp technique, we recorded GABAergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs) from mechanically isolated rat PAG neurons in the presence of 300 nM tetrodotoxin and 20 µM dl-2-amino-5-phosphonovaleric acid under voltage-clamp conditions. Kainic acid at a 10 µM concentration significantly increased the frequency of GABAergic mIPSCs without affecting their amplitude, suggesting that kainic acid acts presynaptically to enhance spontaneous GABA release. The kainic acid-induced increase in mIPSC frequency was completely blocked by CNQX, a selective AMPA/kainate receptor antagonist. While neither AMPA nor NMDA affected GABAergic mIPSC frequency, ATPA, a selective agonist of GluR5-containing kainate receptors, increased GABAergic mIPSC frequency in a concentration-dependent manner. The kainic acid-induced increase in mIPSC frequency was completely suppressed either in the presence of 100 µM Cd 2+, a general voltage-dependent Ca 2+ channel (VDCC) blocker, or in the Na +-free external solution. These results suggest that presynaptic kainate receptors have a low permeability to Ca 2+, and that their activation elicits a presynaptic depolarization large enough to activate presynaptic VDCCs. Presynaptic kainate receptors on GABAergic nerve terminals appear to modulate GABAergic transmission, and in doing so may play an important role in the regulation of PAG neuron excitability.

Modulation of the aqueous extract of Bupleuri radix on glycine-induced current in the acutely dissociated rat periaqueductal gray neurons

SUMMARY Bupleuri radix (Umbelliferae), the dried root of Bupleurum Chinense DC, has been clinically used tomitigate pain sensation. The descending pain control system consists of three major components,and modulation of pain in the periaqueductal gray is the most extensively studied descendingpain control system. However, the relation of Bupleuri radix on the descending pain controlsystem has not been clarified. In the present study, modulation of the aqueous extract of Bupleuriradix on glycine-induced ion current in the acutely dissociated periaqueductal gray neurons wasinvestigated by using nystatin-perforated patch-clamp technique under voltage-clamp condition.In the present results, the glycine-induced ion current was significantly suppressed by 0.1 mg/mlBupleuri radix, while treatment with 10 -5 M naltrexone, opioid receptor antagonist, alleviatedBupleuri radix-induced inhibition on glycine-induced ion current. The present study showed thatthe aqueous extract of Bupleuri radix may activate descending pain control system throughinhibition on glycine-induced ion current in the periaqueductal gray neurons and this effect ismediated by opioid receptors.Key words: Bupleuri radix; Glycine; Periaqueductal gray; Naltrexone; Patch Clamp

Modulation of Amygdalin on Glycine- and Glutamate-induced Ion Currents in Rat Periaqueductal Gray Neurons

Amygdalin is known as vitamain B17, and it was called laetrile. Amygdalin is com posed of two molecules of glucose, one molecule of benzaldehyde which induces an analgesic action, and one molecule of hydrocyanic acid which is an anti-neoplastic compound. Amygdalin had been used to treat cancers and relieve pain. In order to evaluate whether the analgesic action of amygdalin is related with descending pain control system, we performed patch clamp study. In the present study, the modulatory effects of amygdalin on glycine- and glutamate-induced ion currents in periaqueductal gray (PAG) neurons were investigated using the nystatin-perforated patch clamp method. Continuous application of lipopolysaccharides (LPS) on PAG neurons resulted in increased glycine-induced ion current, and in decreased glutamate-induced ion current. In contrast, continuous application of amygdalin with LPS resulted in decreased glycine-induced ion current increased by LPS, and increased glutamateinduced ion current decreased by LPS in concentration- and time-dependent fashion. These results demonstrate that amygdalin modulates neuronal activity of PAG by modulation of glycine and glutamate. Based on the present results, it can be suggested that amygdalin participates in the regulation of the descending pain control system in the level of PAG neurons. The present study demonstrated that activation of the descending pain control system is one of the possible analgesic mechanisms of amygdalin. words: cyclooxygenase-2, periaqueductal gray neurons (PAG), glycine, glutamate, patch clamp, amygdalin

Cholinergic modulation of periaqueductal grey neurons: Does it contribute to epileptogenesis after organophosphorus nerve agent intoxication?

Previous work has shown that a single focal microinjection of the unselective cholinergic agonist, carbachol, into the periaqueductal grey (PAG) of the midbrain is sufficient to induce forebrain seizures in rats. In order to determine the cholinergic mechanisms underlying epileptogenesis at the cellular and network level of the PAG, we performed whole-cell recordings from rat PAG neurons in vitro and examined how the activation of muscarinic and nicotinic receptors modulates cellular excitability and synaptic responses. Stimulation of muscarinic receptors produced either a pirenzepine-sensitive depolarization (40% of PAG neurons), or a gallamine-sensitive hyperpolarization (20%), suggesting the involvement of M1 and M2 receptors, respectively. In the remaining neurons (40%), no change was observed. Voltage-clamp recordings showed that muscarinic depolarization resulted from the inhibition of a resting K + current, in part accompanied by simultaneous activation of a presumed non-selective cation current. Muscarinic hyperpolarization was caused by the activation of a G protein-coupled, inwardly rectifying K + current. Stimulation of muscarinic receptors enhanced the frequency of spontaneous inhibitory postsynaptic currents (IPSCs), but strongly suppressed evoked IPSCs. In addition, nicotine almost doubled the frequency of miniature IPSCs. Based on our findings and the network properties of the PAG, we advance a scenario in which excessive stimulation of cholinergic receptors would substantially contribute to generalized seizures after organophosphorus nerve agent poisoning.

Postsynaptic actions of substance P on rat periaqueductal grey neurons in vitro

The postsynaptic actions of substance P on rat midbrain periaqueductal grey (PAG) neurons were examined using whole-cell patch-clamp recordings in brain slices. Substance P produced an inward current in a subpopulation (60%) of PAG neurons. The substance P induced current was concentration dependent (EC 50=27 nM) and was reduced by the NK1, NK2 and NK3 antagonists L-732,138 (20 μM), GR 159897 (3 μM) and SB 218795 (3 μM). The selective NK1, NK2 and NK3 agonists [Sar 9,Met(O 2) 11]-Substance P (100 nM), GR 64349 (300–500 nM) and senktide (300 nM) also produced inward currents in subpopulations of neurons. A greater proportion of substance P-sensitive neurons (70%) than substance P-insensitive neurons (31%) responded to the μ/δ opioid agonist met-enkephalin (10 μM). Substance P reduced the outward current produced by met-enkephalin. The reversal potential of the substance P induced current varied from −5 mV to below −140 mV in the absence of met-enkephalin, and was −105 mV in the presence of met-enkephalin. These results indicate that substance P acts via NK1, NK2 and NK3 receptors to excite subpopulations of opioid-sensitive and insensitive PAG neurons by increasing a non-selective cation conductance and by reducing a K + current. In addition, substance P has anti-opioid actions that are largely mediated by a reduction in the opioid induced K + current.

Multiple metabotropic glutamate receptor subtypes modulate GABAergic neurotransmission in rat periaqueductal grey neurons in vitro

The effect of metabotropic glutamate receptor (mGluR) activation on GABAergic synaptic transmission in rat periaqueductal grey (PAG) neurons was examined using whole-cell patch-clamp recordings in brain slices. The selective groups I, II and III mGluR agonists DHPG (10–30 μM), DCG-IV (1–3 μM) and L-AP4 (10–30 μM) inhibited electrically evoked GABA A mediated inhibitory postsynaptic currents (IPSCs) in all PAG neurons tested. DCG-IV and L-AP4 also reduced the frequency of spontaneous IPSCs, while DHPG produced both increases and decreases in spontaneous IPSC frequency in a dose dependent manner. In the presence of TTX, DHPG, DCG-IV and L-AP4 all reduced the frequency of spontaneous miniature IPSCs, but had no effect on their amplitudes. The DHPG, DCG-IV and L-AP4 effects on miniature IPSCs were dose dependent (EC 50s=1.4, 0.055 and 0.52 μM, respectively) and were reduced by the selective mGluR antagonists MCPG, EGLU and MSOP, respectively. These results indicate that GABAergic synaptic transmission within the PAG is reduced by groups I, II and III mGluR activation via a presynaptic mechanism and is increased by group I mGluR activation via an action potential dependent mechanism. The finding of convergent groups I, II and III mGluR-mediated inhibition of synaptic transmission is novel and indicates that all groups of mGluRs have the potential to modulate the constellation of analgesic, behavioural and autonomic functions within the PAG.

Modulation of Corydalis tuber on glycine-induced ion current in acutely dissociated rat periaqueductal gray neurons.

Traditionally, Corydalis tuber has been used for the control of pain including headache, stomach ache, and neuralgia. In the present study, modulation of the Corydalis tuber on glycine-activated ion current in the acutely dissociated periaqueductal gray (PAG) neurons was studied by a nystatin-perforated patch-clamp technique. High concentrations of Corydalis tuber elicited ion current, which was suppressed by strychnine application, while low concentrations of Corydalis tuber reduced glycine-induced ion current in the PAG neurons. Inhibitory action of Corydalis tuber on glycine-activated ion current was partially abolished by treatment with naltrexone, a non-selective opioid antagonist. Application of N-methylmalemide (NEM), a sulfhydryl alkylating agent, also partially abolished the inhibitory action of Corydalis tuber on glycine-activated ion current in the PAG neurons. These results suggest that the inhibitory effect of Corydalis tuber on glycine-activated ion current in the PAG neurons is one of the analgesic mechanisms of the Corydalis tuber.

Modulation of Chelidonii herba on glycine-activated and glutamate-activated ion currents in rat periaqueductal gray neurons

Background: Chelidonii herba is classified as Papaver somniferum L. Aqueous extract from C. herba is traditionally used for disorders with symptoms like pain, bloating, abdominal cramp after meals. Methods: Modulation of C. herba on glycine-activated and glutamate-activated ion currents in the acutely dissociated periaqueductal gray (PAG) neurons was investigated by the nystatin-perforated patch-clamp technique. Results: C. herba inhibited glycine-activated ion current and increased glutamate-activated ion current. C. herba-induced inhibition on glycine-activated ion current is implicated in opioid receptors and GTP-binding proteins (G-proteins). Increased glutamate-activated ion current induced by C. herba is linked neither by opioid receptors nor GTP-binding proteins. Conclusions: Suppressed glycine-induced response and elevated glutamate-induced response by C. herba may increase neuronal excitability in PAG, results in activation of descending pain control system, and this mechanism can be suggested as one of the analgesic actions of C. herba.

Developmental changes in the alpha-adrenergic responses of rat periaqueductal grey neurons.

The postnatal changes in alpha-adrenoceptor mediated postsynaptic actions in neurons of the rat midbrain periaqueductal grey (PAG) were examined using whole cell patch clamping techniques. Noradrenaline produced an alpha1-adrenoceptor-mediated inward current which was less in younger (P9-12) than in older rats (P21-30). The alpha1-adrenoceptor response increased between postnatal days 13 and 16. In contrast, alpha2-adrenoceptor, GABA-B and mu-opioid receptor-mediated outward currents remained unchanged between P7 and P30. These observations suggest that alpha1-adrenoceptor responses in the PAG undergo significant postnatal developmental upregulation. Thus, catecholaminergic modulation of the autonomic and nociceptive functions of the PAG are likely to undergo significant postnatal alterations.

Modulation of cyclooxygenase-2 on glycine- and glutamate-induced ion currents in rat periaqueductal gray neurons

Cyclooxygenase (COX) is a key enzyme in the conversion of arachidonic acid to prostaglandins. Two isoforms of COX are known: COX-1 and COX-2. In the present study, the modulatory effect of COX-2 on glycine- and glutamate-induced ion currents in periaqueductal gray (PAG) neurons was investigated using the nystatin-perforated patch clamp method. Continuous application of lipopolysaccharides on PAG neurons resulted in increased glycine-induced ion current and decreased glutamate-induced ion current. In contrast, continuous application of celecoxib, selective COX-2 inhibitor, resulted in decreased glycine-induced ion current and increased glutamate-induced ion current. These results demonstrate that COX-2 modulates neuronal activity of PAG, and it can be suggested that COX-2 participates in the regulation of the descending pain control system in the level of PAG neurons.