The Role of Descending Noradrenergic and Serotoninergic Pathways in the Modulation of Nociception: Focus on Receptor Multiplicity

Millan, Mark J.

doi:10.1007/978-3-642-60777-6_15

Cited by 46 publications

(52 citation statements)

References 395 publications

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“…6 and 7). The effectiveness of the 5-HT 1 receptor agonists in increasing bladder capacity and decreasing threshold volume is in line with the well known antinociceptive properties of serotonin (Millan, 1997), and their abundance in the dorsal horn of the spinal cord (Thor et al, 1993;Millan, 1997) is in accord with their hypothesized action on the sensory limb of the micturition reflex.…”

Section: Discussionsupporting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

“…Serotonin is antinociceptive (Millan, 1997), perhaps largely through actions at 5-HT 1A , 5-HT 1B , and 5-HT 1D receptors, all of which are abundant in the dorsal horn of the spinal cord (Thor et al, 1993;Millan, 1997). Most spinal serotonergic terminals originate from bulbospinal midbrain raphe neurons, and spinal cord injury results in the loss of these terminals.…”

mentioning

confidence: 99%

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Inhibition of Bladder Activity by 5-Hydroxytryptamine1 Serotonin Receptor Agonists in Cats with Chronic Spinal Cord Injury

Gu¹,

Olejar²,

Reiter³

et al. 2004

The Journal of Pharmacology and Experimental Therapeutics

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The serotonin (5-hydroxytryptamine 1A ) 5-HT 1A receptor agonist 8-OH-DPAT [(R)-(ϩ)-8-hydroxy-2-(di-n-propylamino)tetralin] inhibits bladder activity under nociceptive but not innocuous conditions in cats with an intact spinal cord, suggestive of an effect on primary afferent C fibers or their targets. Because C fibers play a key role in reflex micturition in chronic spinal cord injury (SCI), we investigated the effect of 8-OH-DPAT on micturition in SCI cats. We also investigated GR-46611 (3-[3-(2-dimethylaminoethyl)-1H-indol-5-yl]-N-(4-methoxybenzyl)acrylamide), which has agonist activity predominantly at 5-HT 1B and 5-HT 1D receptors but also at the 5-HT 1A receptor. Chloraloseanesthetized cats were catheterized through the bladder dome for saline-filling cystometry. Dose-response curves for i.v. 8-OH-DPAT (0.3-30 g/kg) and GR-46611 (0.03-300 g/kg) were followed in three cases each by 5-HT 1A antagonist WAY-100635 [N-tert-butyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide] at 300 g/kg. Threshold volume, capacity, residual volume, micturition volume, and arterial pressure were measured. Intact cats showed few significant changes in cystometric variables. SCI cats responded to both 8-OH-DPAT and GR-46611 with dose-dependent increases in threshold volume, capacity, and residual volume, significant at Ն10 g/kg for 8-OH-DPAT and at Ն3 g/kg for GR-46611. Effects of 8-OH-DPAT but not GR-46611 were largely reversed by WAY-100635. Both 5-HT 1A and 5-HT 1B/1D agonists may offer a promising means of reducing bladder hyperactivity and increasing bladder capacity in patients with chronic SCI.With spinal cord injury (SCI) rostral to the lumbosacral level, the most common constellation of lower urinary tract symptoms is loss of voluntary control of micturition, bladder hyperactivity mediated by spinal reflex pathways, and hyperreflexia or spasticity of the external urethral sphincter (EUS), with bladder and EUS activity commonly being dyssynchronous (bladder-sphincter dyssynergia) (Arnold, 1999;Madersbacher et al., 1999;Yoshimura et al., 2000). The patient is thus left in a state of unbalanced reflex incontinence, for which the management of choice is currently intermittent self-catheterization (Madersbacher et al., 1999). Pharmacotherapy that reduces bladder hyperactivity, improves EUS function, and increases functional bladder capacity could be beneficial in maintaining continence between catheterizations, reducing kidney damage that results from high intravesical pressure, and reducing autonomic dysreflexia associated with bladder hyperreflexia.Primary afferent C fibers and the second order neurons with which they communicate are attractive targets for pharmacotherapy. Whereas mechanoreceptive A␦ fibers participate in the normal spinobulbospinal micturition reflex, C fibers are generally silent during bladder filling in normal animals and are activated only in nociceptive conditions (de Groat et al., 1990). In chronic SCI, the spinobulbospinal reflex is lost and C fibers participate in the purely spi...

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Section: Discussionsupporting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Inhibition of Bladder Activity by 5-Hydroxytryptamine1 Serotonin Receptor Agonists in Cats with Chronic Spinal Cord Injury

Gu¹,

Olejar²,

Reiter³

et al. 2004

The Journal of Pharmacology and Experimental Therapeutics

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“…The ascending ventral and dorsal noradrenergic bundles originating mainly in neurons located in the A1/A2 and C1/C2 cell groups reach in various parts of the forebrain and participate in behavioral and neuroendocrine response to the painful stimuli (Palkovits 2002). In addition to ascending catecholamine pathways, descending pathways also arise in the lower brainstem and participate in pain inhibition (Millan 1997;Willis and Westlund 1997;Barnes and Sharp 1999;Millan 2002). The spinal cord is directly innervated by A1/C1, A5, A6 and A7 catecholamine groups of the brainstem (Kwiat and Basbaum 1992;Tavares et al 1996;Westlund and Craig 1996).…”

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

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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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Health insurance coverage and cost barriers to needed medical care among U.S. adult cancer survivors age <65 years

Sabatino

Coates

Uhler

et al. 2006

Cancer

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The spinal dorsal horn receives a dense innervation of noradrenaline‐containing fibers that originate from pontine neurons in the A5, locus coeruleus (LC), and A7 cell groups. These pontospinal neurons are believed to constitute a component of the endogenous analgesic system. We used an adenoviral vector with a catecholaminergic‐selective promoter (AVV‐PRS) to retrogradely label the noradrenergic neurons projecting to the lumbar (L4–L5) dorsal horn with enhanced green fluorescent protein (EGFP) or monomeric red fluorescent protein (mRFP). Retrogradely labeled neurons (145 ± 12, n = 14) were found in A5‐12%, LC‐80% and A7‐8% after injection of AVV‐PRS‐EGFP to the dorsal horn of L4–L5. These neurons were immunopositive for dopamine β‐hydroxylase, indicating that they were catecholaminergic. Retrograde labeling was optimal 7 days after injection, persisted for over 4 weeks, and was dependent on viral vector titer. The spinal topography of the noradrenergic projection was examined using EGFP‐ and mRFP‐expressing adenoviral vectors. Pontospinal neurons provide bilateral innervation of the cord and there was little overlap in the distribution of neurons projecting to the cervical and lumbar regions. The axonal arbor of the pontospinal neurons was visualized with GFP immunocytochemistry to show projections to the inferior olive, cerebellum, thalamus, and cortex but not to the hippocampus or caudate putamen. Formalin testing evoked c‐fos expression in these pontospinal neurons, suggesting that they were nociresponsive (A5‐21%, LC‐16%, and A7‐26%, n = 8). Thus, we have developed a viral vector‐based strategy to selectively, retrogradely target the pontospinal noradrenergic neurons that are likely to be involved in the descending control of nociception. J. Comp. Neurol. 512:141–157, 2009. © 2008 Wiley‐Liss, Inc.

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The Role of Descending Noradrenergic and Serotoninergic Pathways in the Modulation of Nociception: Focus on Receptor Multiplicity

Cited by 46 publications

References 395 publications

Inhibition of Bladder Activity by 5-Hydroxytryptamine1 Serotonin Receptor Agonists in Cats with Chronic Spinal Cord Injury

Inhibition of Bladder Activity by 5-Hydroxytryptamine1 Serotonin Receptor Agonists in Cats with Chronic Spinal Cord Injury

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

Health insurance coverage and cost barriers to needed medical care among U.S. adult cancer survivors age <65 years

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