Interactions Between Cardiovascular and Pain Regulatory Systems

Randich, Alan

doi:10.1007/978-1-4684-9184-5_12

Cited by 63 publications

(102 citation statements)

References 104 publications

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“…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). Furthermore, catecholamine-induced elevations in blood pressure have been shown to produce analgesia through the stimulation of arterial baroreceptors Randich and Maixner 1984;Zamir and Maixner 1986). Taken together, these findings are in line with the view that catecholamines can exert divergent influences on nociception as a function of localization and net influence on neuronal excitability.…”

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

confidence: 75%

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

Nackley

Tan

Fecho

et al. 2007

Pain

257

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 Adresupporting

confidence: 75%

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

Nackley

Tan

Fecho

et al. 2007

Pain

257

200

View full text Add to dashboard Cite

show abstract

“…After denervation, the blood pressure elevation slightly increased the avoidance behavior. These results were replicated by Randich and Maixner (1984), who also controlled for the heart rate changes by additionally applying atropine and blocking the parasympathetically mediated heart rate decrease. Again, an inhibition of pain avoidance behavior in response to blood pressure elevation was found only in animals with baroreceptors left intact.…”

Section: Experimentally Induced Hypertension and Pain (Animal Studies)mentioning

confidence: 71%

“…Furthermore, the application of Phenylephrine in conjunction with a vagal blocker (atropine) may be used to eliminate the baroreceptor reflex and thus exclude indirect effects of baroreceptor firing as a consequence of changes in blood flow e.g. to muscles, to the viscera or to the brain (e.g., Randich and Maixner, 1984). In human experiments, however, such stringent manipulations go beyond the ethical limits.…”

Section: Pharmacological Manipulations Of the Blood Pressurementioning

confidence: 99%

Psychophysiology of arterial baroreceptors and the etiology of hypertension

Rau

Elbert

2001

Biological Psychology

161

143

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Arterial baroreceptors are sensitive to blood pressure dependent blood vessel dilation. They play a key role in the short term regulation of blood pressure. Their impact on psychological and psychophysiological aspects is of increasing interest. The review focuses on experimental techniques for the controlled baroreceptor manipulation. Results from the application of these techniques show that baroreceptor activation influences the cardiovascular system as well as central nervous functioning: Behavioral and electrophysiological measures of arousal, low level reflexes and pain responses are modulated through baroreceptor manipulation. The observation of an overall dampening ('barbiturate like') effect of baroreceptor activity led Dworkin et al. formulate the theory of learned hypertension: Subjects might experience blood pressure dependent baroreceptor activation as stress and pain relieving. High blood pressure periods become negatively reinforced. Phasic high blood pressure might develop as a coping strategy. Data from a longitudinal human study supporting this theory are reported.

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“…[5][6][7] Furthermore, there is evidence to suggest that the negative association between blood pressure and pain is not just a phenomenon observed in those with hypertension, but represents a continuous association that extends into the normotensive range, such that as blood pressure increases pain sensitivity decreases. [8][9][10][11][12] Although there is currently little direct evidence, there are several reasons to suspect that this blood pressure-pain association, known as blood pressure-related hypoalagesia, might be related to silent ischaemia.…”

Section: Introductionmentioning

confidence: 99%

“…13,14 Reductions in pain sensitivity have been associated with both sustained and acute increases in blood pressure in experimental animals as well as humans. [5][6][7][15][16][17] Blood pressure-related hypoalagesia has been demonstrated with naturalistic, clinical pain as well as in response to well-controlled experimental pain stimuli. [18][19][20] Finally, data from a previous study found an association between resting blood pressure, 21 exercise blood pressure 22 and silent ischaemia in cardiac patients undergoing treadmill exercise.…”

Section: Introductionmentioning

confidence: 99%

The role of ischaemia and pain in the blood pressure response to exercise stress testing in patients with coronary heart disease

et al. 2006

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Silent myocardial ischaemia is a common phenomenon in patients with coronary heart disease. However, very little is known about the underlying mechanisms of silent ischaemia. One potential pathway that may contribute to this absence of pain is increased blood pressure. The main aim of the current study was to assess the associations among blood pressure, pain and ischaemia in patients undergoing a standard exercise stress test. We hypothesized that patients who experienced chest pain during exercise would have lower baseline and peak blood pressures compared to those who did not experience chest pain. A total of 1355 patients (418 women) who underwent a single-photon emission computed tomography treadmill exercise stress test and had not experienced a cardiac event in the past 2 weeks participated in the current study. Myocardial perfusion defects were assessed at rest and during the stress challenge. Systolic blood pressure (SBP), diastolic blood pressure, heart rate (HR) and rate pressure product (RPP) were assessed during rest and at peak exercise. There were no main effects of either pain or ischaemia on the baseline cardiovascular variables. Peak exercise data revealed main effects of pain on SBP, RPP and HR, and main effects of ischaemia on SBP and RPP, controlling for age, sex, baseline level, medication status and cardiac history. These findings suggest that acute rather than chronic increases in blood pressure may be one mechanism to explain the phenomena of silent myocardial ischaemia in cardiac patients, and may potentially provide a target for future treatment strategies.

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Interactions Between Cardiovascular and Pain Regulatory Systems

Cited by 63 publications

References 104 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

Psychophysiology of arterial baroreceptors and the etiology of hypertension

The role of ischaemia and pain in the blood pressure response to exercise stress testing in patients with coronary heart disease

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