Bidirectional modulation of nociception by GABA neurons in the dorsolateral pontine tegmentum that tonically inhibit spinally projecting noradrenergic A7 neurons

Nuseir, Khawla; Proudfit, Herbert K.

doi:10.1016/s0306-4522(99)00603-x

Cited by 58 publications

(40 citation statements)

References 71 publications

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“…In the A7 area, nonNAergic interneurons are scattered among the NAergic neurons and make synaptic contacts with them (Min et al 2008b). These non-NAergic neurons are presumed to be GABAergic (Bajic et al 2001;Holden and Proudfit 1998;Nuseir and Proudfit 2000) and are proposed to be subject to inhibitory control by enkephalin released from neurons in the RVM and ventrolateral PAG. Activation of these nuclei of descending analgesic pathways would relieve the tonic inhibition of NAergic neurons in the A7 area, which, in turn, would increase NA release in the dorsal spinal cord (Bajic et al 2001;Holden et al 1999;Nuseir and Proudfit 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, axonal terminals from the RVM/PAG synapse not only on NAergic A7 neurons but also on local GABAergic interneurons (Bajic et al 2001). Microinjection of bicuculline, a GABA A receptor (GABA A R) antagonist, into the A7 area modulates nociceptive behavior, and this effect is abolished by intrathecal injection of adrenoceptor antagonists (Nuseir and Proudfit 2000). On the basis of these results, Nuseir and Proudfit (2000) proposed that NAergic A7 neurons are subject to tonic inhibition by local GABAergic interneurons, which are inhibited by inhibitory neurotransmitters released from axon terminals from the PAG/RVM, thus relieving the tonic inhibition of the NAergic A7 neurons and promoting NE release in the dorsal horn.…”

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confidence: 99%

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GABA_B receptor-mediated tonic inhibition of noradrenergic A7 neurons in the rat

Wu¹,

Wang²,

Cy³

et al. 2011

Journal of Neurophysiology

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Noradrenergic (NAergic) A7 neurons that project axonal terminals to the dorsal horn of the spinal cord to modulate nociceptive signaling are suggested to receive tonic inhibition from local GABAergic interneurons, which are under the regulation of descending analgesic pathways. In support of this argument, we presently report GABA(B) receptor (GABA(B)R)-mediated tonic inhibition of NAergic A7 neurons. Bath application of baclofen induced an outward current (I(Bac)) in NAergic A7 neurons that was blocked by CGP 54626, a GABA(B)R blocker. The I(Bac) was reversed at about -99 mV, displayed inward rectification, and was blocked by Ba(2+) or Tertipian-Q, showing it was mediated by G protein-activated inward-rectifying K(+) (GIRK) channels. Single-cell RT-PCR results suggested that GIRK1/3 heterotetramers might dominate functional GIRK channels in NAergic A7 neurons. Under conditions in which GABA(A) and glycine receptors were blocked, bath application of GABA inhibited the spontaneous firing of NAergic A7 neurons in a dose-dependent manner. Interestingly, CGP 54626 application not only blocked the effect of GABA but also increased the firing rate to 126.9% of the control level, showing that GABA(B)Rs were constitutively active at an ambient GABA concentration of 2.8 μM and inhibited NAergic A7 neurons. GABA(B)Rs were also found at presynaptic excitatory and inhibitory axonal terminals in the A7 area. Pharmacological activation of these GABA(B)Rs inhibited the release of neurotransmitters. No physiological role was found for GABA(B)Rs on excitatory terminals, whereas those on the inhibitory terminals were found to exert autoregulatory control of GABA release.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

GABA_B receptor-mediated tonic inhibition of noradrenergic A7 neurons in the rat

Wu¹,

Wang²,

Cy³

et al. 2011

Journal of Neurophysiology

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“…Many studies have shown a role of the adrenergic descending pathway in the modulation of nociception. For example, spinal administration of NE (Reddy et al 1980;Yaksh 1985;Eisenach et al 1996;Shinomura et al 1999) or electrical stimulation of central noradrenergic cells induced powerful antinociception (Stamford 1995;Nuseir and Proudfit 2000). Further studies found that the antinociceptive effect of NE is mediated by α 2 -adrenoceptors (Howe et al 1983;Fleetwood-Walker et al 1985;Yaksh 1985).…”

Section: Discussionmentioning

confidence: 99%

Electroacupuncture-induced analgesia in a rat model of ankle sprain pain is mediated by spinal α-adrenoceptors

Koo

Lim

Chung

et al. 2008

Pain

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In a previous study, we showed that electroacupuncture (EA) applied to the SI-6 point on the contralateral forelimb produces long-lasting and powerful analgesia in pain caused by ankle sprain in a rat model. To investigate the underlying mechanism of EA analgesia, the present study tested the effects of various antagonists to known endogenous analgesic systems in this model. Ankle sprain was induced in anesthetized rats by overextending their right ankle with repeated forceful plantar flexion and inversion of the foot. When rats developed pain behaviors (a reduction in weight bearing of the affected hind limb), EA was applied to the SI-6 point on the contralateral forelimb for 30 minutes under halothane anesthesia. EA significantly improved the weight-bearing capacity of the affected hind limb for 2 hours, suggesting an analgesic effect. The alpha-adrenoceptor antagonist phentolamine (2 mg/kg, i.p. or 30 μg, i.t.) completely blocked the EA-induced analgesia, whereas naloxone (1 mg/kg, i.p.) and failed to block the effect. These results suggest that EA-induced analgesia is mediated by alpha-adrenoceptor mechanisms. Further experiments showed that intrathecal administration of yohimbine (10 μg), an α 2 -adrenergic antagonist, reduced the EAinduced analgesia in a dose-dependent manner, whereas terazosin (10 μg), an α 1 -adrenergic antagonist, did not produce any effect. These data suggest that the analgesic effect of EA in ankle sprain pain is, at least in part, mediated by spinal α 2 -adrenoceptor mechanisms.

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“…Experimental data suggest that signals produced by formalin-induced chemical and/or inflammatory nociception are under the modulation of the monoaminergic (noradrenergic and serotonergic) descending inhibitory systems (Omote et al 1998). Experiments using electrical or chemical stimulation methods confirmed involvement of A5 and A7 region in modulation of nociceptive processes in the spinal cord (Stamford 1995;Nuseir and Proudfit 2000;Bajic and Commons 2010;Marques-Lopes et al 2010). A5 and A7 neurons act as sympathetic premotor neurons by innervating the intermediolatral cell column in the thoracic spinal cord and activate the sympatho-adrenal system for responding to painful stimuli.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, axons originating in A5-A7 noradrenergic cell groups participate also on descending modulation of transmission of pain at the level of spinal cord (Stamford 1995;Millan 1997Millan , 2002Nuseir and Proudfit 2000).…”

Section: Introductionmentioning

confidence: 99%

Effect of lesions of A5 or A7 noradrenergic cell group or surgical transection of brainstem catecholamine pathways on plasma catecholamine levels in rats injected subcutaneously by formalin

Mravec¹,

Bodnár²,

Uhereczky³

et al. 2012

gpb

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Abstract. The pain-induced activation of the sympatho-adrenal system is modulated by several brain areas, including brainstem catecholamine cell groups. In the present study, we evaluated the effect of bilateral lesions of the A5 or A7 cell groups or bilateral transections of brainstem catecholaminergic pathways on plasma catecholamine levels in Sprague-Dawley rats injected subcutaneously by formalin or saline. Plasma levels of both epinephrine and norepinephrine were slightly elevated after formalin injections within 15-30 min in rats with or without lesions of the A7 catecholamine cell group. However, saline but not formalin elicited a significant increase in plasma epinephrine level in both sham-operated and A5-lesioned groups. It is more likely, that formalin blocks the effect of the handling and the painful injection procedure. In rats with bilateral partial transections of the lower brainstem, formalin was more effective than saline in the elevation of plasma epinephrine and norepinephrine levels at several time-points through the investigation period. Our data indicate the involvement of A5 and A7 norepinephrine neurons and brainstem catecholaminergic pathways in the regulation of the activity of the sympatho-adrenal system during acute painful situations. Their modulatory effect, however, seems to be a very rapid one, short and moderate.

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Bidirectional modulation of nociception by GABA neurons in the dorsolateral pontine tegmentum that tonically inhibit spinally projecting noradrenergic A7 neurons

Cited by 58 publications

References 71 publications

GABA_B receptor-mediated tonic inhibition of noradrenergic A7 neurons in the rat

GABA_B receptor-mediated tonic inhibition of noradrenergic A7 neurons in the rat

Electroacupuncture-induced analgesia in a rat model of ankle sprain pain is mediated by spinal α-adrenoceptors

Effect of lesions of A5 or A7 noradrenergic cell group or surgical transection of brainstem catecholamine pathways on plasma catecholamine levels in rats injected subcutaneously by formalin

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Bidirectional modulation of nociception by GABA neurons in the dorsolateral pontine tegmentum that tonically inhibit spinally projecting noradrenergic A7 neurons

Cited by 58 publications

References 71 publications

GABAB receptor-mediated tonic inhibition of noradrenergic A7 neurons in the rat

GABAB receptor-mediated tonic inhibition of noradrenergic A7 neurons in the rat

Electroacupuncture-induced analgesia in a rat model of ankle sprain pain is mediated by spinal α-adrenoceptors

Effect of lesions of A5 or A7 noradrenergic cell group or surgical transection of brainstem catecholamine pathways on plasma catecholamine levels in rats injected subcutaneously by formalin

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GABA_B receptor-mediated tonic inhibition of noradrenergic A7 neurons in the rat

GABA_B receptor-mediated tonic inhibition of noradrenergic A7 neurons in the rat