Sympathetic facilitation of sustained discharges of polymodal nociceptors

Hu, San-Jue; Zhu, Jianping

doi:10.1016/0304-3959(89)90077-8

Cited by 129 publications

(35 citation statements)

References 14 publications

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“…Additional studies are also required to elucidate the role of peripheral versus central β 2/3 -adrenergic systems in the development of COMT-dependent pain sensitivity. Although epinephrine and norepinephrine have previously been shown to sensitize nociceptors located on small diameter primary afferents in the periphery (Hu and Zhu 1989;Khasar et al 1999b;Shyu et al 1989), elevated levels of central catecholamines are generally associated with descending inhibition of pain via actions at α 2 ARs or D 2 DARs in the spinal dorsal horn (Millan 2002). Antidepressants used extensively in the treatment of persistent pain conditions, are thought to inhibit pain transmission at the spinal level by increasing synaptic levels of norepinephrine and serotonin (Sanchez and Hyttel 1999) as well as by blocking tetrodotoxin-resistant sodium channels (Brau et al 2001).…”

Section: Comt Inhibition Increases Pain Behavior Via β 2 and β 3 Adrementioning

confidence: 99%

Catechol- O -methyltransferase inhibition increases pain sensitivity through activation of both β2- and β3-adrenergic receptors

Nackley

Tan

Fecho

et al. 2007

Pain

256

200

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Catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines, has recently been implicated in the modulation of pain. Our group demonstrated that human genetic variants of COMT are predictive for the development of Temporomandibular Joint Disorder (TMJD) and are associated with heightened experimental pain sensitivity (Diatchenko et al. 2005). Variants associated with heightened pain sensitivity produce lower COMT activity. Here we report the mechanisms underlying COMT-dependent pain sensitivity. To characterize the means whereby elevated catecholamine levels, resulting from reduced COMT activity, modulate heightened pain sensitivity, we administered a COMT inhibitor to rats and measured behavioral responsiveness to mechanical and thermal stimuli. We show that depressed COMT activity results in enhanced mechanical and thermal pain sensitivity. This phenomenon is completely blocked by the nonselective β-adrenergic antagonist propranolol or by the combined administration of selective β 2 -and β 3 -adrenergic antagonists, while administration of β 1 -adrenergic, α-adrenergic, or dopaminergic receptor antagonists fail to alter COMT-dependent pain sensitivity. These data provide the first direct evidence that low COMT activity leads to increased pain sensitivity via a β 2/3 -adrenergic mechanism. These findings are of considerable clinical importance, suggesting that pain conditions resulting from low COMT activity and/or elevated catecholamine levels can be treated with pharmacological agents that block both β 2 -and β 3 -adrenergic receptors. Keywords epinephrine; norepinephrine; catecholamines; allodynia; hyperalgesia; carrageenan Catecholamines and enzymatic pathways that regulate the bioavailability of catecholamines influence persistent pain. Adrenergic systems contribute to the pathogenesis of rheumatoid Corresponding Author: Andrea G Neely, Center for Neurosensory Disorders, School of Dentistry, CB 7450, University of North Carolina, Chapel Hill, NC 27599-7450, Phone: (919) 966-2953, Fax: (919) Email: andrea_nackley@dentistry.unc.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptPain. Author manuscript; available in PMC 2007 July 2. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript arthritis in animals, as denervation of sympathetic noradrenergic fibers (Levine et al. 1986a) and depletion of peripheral epinephrine (Coderre et al. 1990) attenuate arthritic responses. Additionally, chronic administration of β-adrenergic receptor (βAR) agonists produces a painful arthritis-like s...

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Section: Comt Inhibition Increases Pain Behavior Via β 2 and β 3 Adrementioning

confidence: 99%

Catechol- O -methyltransferase inhibition increases pain sensitivity through activation of both β2- and β3-adrenergic receptors

Nackley

Tan

Fecho

et al. 2007

Pain

256

200

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“…2 m/s were classified as C fibers [23,24] . If the amplitude and shape of the action potentials remained the same during the recordings, they were defined as responses from a single C fiber; sometimes collision tests were also used (see below) [24] . Only these single C fibers were studied further.…”

Section: In Vivo Electrophysiological Recording Of Single C Fiber Dismentioning

confidence: 99%

Conduction Failures in Rabbit Saphenous Nerve Unmyelinated Fibers

Zhu¹,

Tang

Wang

et al. 2009

Neurosignals

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Recent experimental and theoretical data indicate that the functional capabilities of axons with specialized structures are much more diverse than traditionally thought. However, few observations were concerned with the main axons without arborization. In the present study, electrical stimulation of the saphenous nerve at different frequencies (2, 5, 10, 20 Hz) was used to test the role of activity-dependent effects on the pattern of action potentials that propagate along individual unmyelinated fibers (C fibers) within the trunk of the saphenous nerve in rabbits. Three basic types of C fiber responses to repetitive stimulation were observed: type-1 fibers showed an entrained response without conduction failure; type-2 fibers discharged with intermittent conduction failures; while only sporadic conduction failures happened in type 3. The failure modality in type-2 and type-3 fibers is closely related to the conductive distance as well as the frequency and duration of stimuli which lead to a critical level of conduction velocity slowing. A novel fluctuation in interspike intervals was always observed immediately before the occurrence of the failures, implying that the fluctuation of conduction velocity is correlated with imminent failures. Both the 4-aminopyridine-sensitive potassium current and hyperpolarization-activated cation current were recognized to be involved in the regulation of conduction failure patterns. The results confirmed, at least in part, the existence of conduction failures in the main axon of C fibers, suggesting that axonal operations may also be determinants for adaptation phenomenon and information processing in peripheral nervous system.

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“…Action potentials were amplified (VC-11, Nihon Kohden) and recorded via a computer A/D board with a signal sampling rate of 10 kHz. The C-fiber was identified as a polymodal nociceptor when C-fiber firings in the receptive field were evoked by 100 g Von Frey hair as well as a small cotton ball with hot water (55-60°C) (Hu and Zhu 1989). In the present study, all of the C-fibers reported were polymodal nociceptive only.…”

Section: Animal Model Of Diabetic Neuropathic Pain and Behavioral Testsmentioning

confidence: 46%

α-Dendrotoxin-sensitive Kv1 channels contribute to conduction failure of polymodal nociceptive C-fibers from rat coccygeal nerve

Wang

Zhang

et al. 2016

Journal of Neurophysiology

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Sympathetic facilitation of sustained discharges of polymodal nociceptors

Cited by 129 publications

References 14 publications

Catechol- O -methyltransferase inhibition increases pain sensitivity through activation of both β2- and β3-adrenergic receptors

Catechol- O -methyltransferase inhibition increases pain sensitivity through activation of both β2- and β3-adrenergic receptors

Conduction Failures in Rabbit Saphenous Nerve Unmyelinated Fibers

α-Dendrotoxin-sensitive Kv1 channels contribute to conduction failure of polymodal nociceptive C-fibers from rat coccygeal nerve

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